Protein phosphatase 2A1 is the major enzyme in vertebrate cell extracts that dephosphorylates several physiological substrates for cyclin- dependent protein kinases

P Ferrigno, TA Langan and P Cohen

Department of Biochemistry, University of Dundee, Tayside, Scotland, United Kingdom.

Okadaic acid (2 nM) inhibited by 80-90% the protein phosphatase activities in diluted extracts of rat liver, human fibroblasts, and Xenopus eggs acting on three substrates (high mobility group protein- I(Y), caldesmon and histone H1) phosphorylated by a cyclin-dependent protein kinase (CDK) suggesting that a type-2A phosphatase was responsible for dephosphorylating each protein. This result was confirmed by anion exchange chromatography of rat liver and Xenopus extracts, which demonstrated that the phosphatases acting on these substrates coeluted with the two major species of protein phosphatase 2A, termed PP2A1 and PP2A2. When matched for activity toward glycogen phosphorylase, PP2A1 was five- to sevenfold more active than PP2A2 and 35-fold to 70-fold more active than the free catalytic subunit (PP2Ac) toward the three CDK-labeled substrates. Protein phosphatases 1, 2B, and 2C accounted for a negligible proportion of the activity toward each substrate under the assay conditions examined. The results suggest that PP2A1 is the phosphatase that dephosphorylates a number of CDK substrates in vivo and indicate that the A and B subunits that are associated with PP2Ac in PP2A1 accelerate the dephosphorylation of CDK substrates, while suppressing the dephosphorylation of most other proteins. The possibility that PP2A1 activity is regulated during the cell cycle is discussed.

Volume 4, Issue 7, pp. 669-677, 07/01/1993
Copyright © 1993 by The American Society for Cell Biology

This article has been cited by other articles:

				P. V. Castilho, B. C. Williams, S. Mochida, Y. Zhao, and M. L. Goldberg The M Phase Kinase Greatwall (Gwl) Promotes Inactivation of PP2A/B55{delta}, a Phosphatase Directed Against CDK Phosphosites Mol. Biol. Cell, November 15, 2009; 20(22): 4777 - 4789. [Abstract] [Full Text] [PDF]

				D. A. Bennin, A. S. A. Don, T. Brake, J. L. McKenzie, H. Rosenbaum, L. Ortiz, A. A. DePaoli-Roach, and M. C. Horne Cyclin G2 Associates with Protein Phosphatase 2A Catalytic and Regulatory B' Subunits in Active Complexes and Induces Nuclear Aberrations and a G1/S Phase Cell Cycle Arrest J. Biol. Chem., July 19, 2002; 277(30): 27449 - 27467. [Abstract] [Full Text] [PDF]

				M. S. Feschenko, E. Stevenson, A. C. Nairn, and K. J. Sweadner A Novel cAMP-Stimulated Pathway in Protein Phosphatase 2A Activation J. Pharmacol. Exp. Ther., July 1, 2002; 302(1): 111 - 118. [Abstract] [Full Text] [PDF]

				J. Holst, A. T.R. Sim, and R. I. Ludowyke Protein Phosphatases 1 and 2A Transiently Associate with Myosin during the Peak Rate of Secretion from Mast Cells Mol. Biol. Cell, March 1, 2002; 13(3): 1083 - 1098. [Abstract] [Full Text] [PDF]

				G. M. Venturi, A. Bloecher, T. Williams-Hart, and K. Tatchell Genetic Interactions Between GLC7, PPZ1 and PPZ2 in Saccharomyces cerevisiae Genetics, May 1, 2000; 155(1): 69 - 83. [Abstract] [Full Text]

				M. Lowe, N. K. Gonatas, and G. Warren The Mitotic Phosphorylation Cycle of the Cis-Golgi Matrix Protein Gm130 J. Cell Biol., April 17, 2000; 149(2): 341 - 356. [Abstract] [Full Text] [PDF]

				C. S. Moreno, S. Park, K. Nelson, D. Ashby, F. Hubalek, W. S. Lane, and D. C. Pallas WD40 Repeat Proteins Striatin and S/G2 Nuclear Autoantigen Are Members of a Novel Family of Calmodulin-binding Proteins That Associate with Protein Phosphatase 2A J. Biol. Chem., February 25, 2000; 275(8): 5257 - 5263. [Abstract] [Full Text] [PDF]

				E. Ogris, I. Mudrak, E. Mak, D. Gibson, and D. C. Pallas Catalytically Inactive Protein Phosphatase 2A Can Bind to Polyomavirus Middle Tumor Antigen and Support Complex Formation with pp60c-src J. Virol., September 1, 1999; 73(9): 7390 - 7398. [Abstract] [Full Text]

				P. Turowski, T. Myles, B. A. Hemmings, A. Fernandez, and N. J. C. Lamb Vimentin Dephosphorylation by Protein Phosphatase 2A Is Modulated by the Targeting Subunit B55 Mol. Biol. Cell, June 1, 1999; 10(6): 1997 - 2015. [Abstract] [Full Text]

				M. F. Santoro, R. R. Annand, M. M. Robertson, Y.-W. Peng, M. J. Brady, J. A. Mankovich, M. C. Hackett, T. Ghayur, G. Walter, W. W. Wong, et al. Regulation of Protein Phosphatase 2A Activity by Caspase-3 during Apoptosis J. Biol. Chem., May 22, 1998; 273(21): 13119 - 13128. [Abstract] [Full Text] [PDF]

				C. Csortos, S. Zolnierowicz, E. Bakó, S. D. Durbin, and A. A. DePaoli-Roach High Complexity in the Expression of the B` Subunit of Protein Phosphatase 2A(0) J. Biol. Chem., February 2, 1996; 271(5): 2578 - 2588. [Abstract] [Full Text] [PDF]

				H. Snaith, C. Armstrong, Y Guo, K Kaiser, and P. Cohen Deficiency of protein phosphatase 2A uncouples the nuclear and centrosome cycles and prevents attachment of microtubules to the kinetochore in Drosophila microtubule star (mts) embryos J. Cell Sci., January 12, 1996; 109(13): 3001 - 3012. [Abstract] [PDF]

				J. Paulson, J. Patzlaff, and A. Vallis Evidence that the endogenous histone H1 phosphatase in HeLa mitotic chromosomes is protein phosphatase 1, not protein phosphatase 2A J. Cell Sci., January 6, 1996; 109(6): 1437 - 1447. [Abstract] [PDF]

				C Jones and C Smythe Activation of the Xenopus cyclin degradation machinery by full-length cyclin A J. Cell Sci., January 5, 1996; 109(5): 1071 - 1079. [Abstract] [PDF]

				B. McCright and D. M. Virshup Identification of a New Family of Protein Phosphatase 2A Regulatory Subunits J. Biol. Chem., November 3, 1995; 270(44): 26123 - 26128. [Abstract] [Full Text] [PDF]

				R. Mayer-Jaekel, H Ohkura, P Ferrigno, N Andjelkovic, K Shiomi, T Uemura, D. Glover, and B. Hemmings Drosophila mutants in the 55 kDa regulatory subunit of protein phosphatase 2A show strongly reduced ability to dephosphorylate substrates of p34cdc2 J. Cell Sci., January 9, 1994; 107(9): 2609 - 2616. [Abstract] [PDF]

				K Shiomi, M Takeichi, Y Nishida, Y Nishi, and T Uemura Alternative cell fate choice induced by low-level expression of a regulator of protein phosphatase 2A in the Drosophila peripheral nervous system Development, January 6, 1994; 120(6): 1591 - 1599. [Abstract] [PDF]